Dopamine innervation of a subclass of local circuit neurons in monkey prefrontal cortex: ultrastructural analysis of tyrosine hydroxylase and parvalbumin immunoreactive structures

Sesack, Susan R.; Hawrylak, Valerie A.; Melchitzky, Darlene S.; Lewis, David A.

doi:10.1093/cercor/8.7.614

Cited by 116 publications

(68 citation statements)

References 68 publications

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“…Ultrastructural studies indicate that dopamine axons in the PFC form synapses with interneurons (Smiley and GoldmanRakic, 1993;Sesack et al, 1995b), particularly PV-containing cells (Sesack et al, 1998). The finding that PV-containing interneurons are the major target of dopamine/neurotensin axons is consistent with our finding that NTR1 is mainly expressed by PV interneurons, although we also found that CB-and some CR-li cells express NTR1.…”

Section: Expression Of Ntr1 On Gaba Interneuronssupporting

confidence: 90%

Neurotensin Activates GABAergic Interneurons in the Prefrontal Cortex

Petrie¹,

Schmidt²,

Bubser³

et al. 2005

J. Neurosci.

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Converging data suggest a dysfunction of prefrontal cortical GABAergic interneurons in schizophrenia. Morphological and physiological studies indicate that cortical GABA cells are modulated by a variety of afferents. The peptide transmitter neurotensin may be one such modulator of interneurons. In the rat prefrontal cortex (PFC), neurotensin is exclusively localized to dopamine axons and has been suggested to be decreased in schizophrenia. However, the effects of neurotensin on cortical interneurons are poorly understood. We used in vivo microdialysis in freely moving rats to assess whether neurotensin regulates PFC GABAergic interneurons. Intra-PFC administration of neurotensin concentration-dependently increased extracellular GABA levels; this effect was impulse dependent, being blocked by treatment with tetrodotoxin. The ability of neurotensin to increase GABA levels in the PFC was also blocked by pretreatment with 2-[1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxyphenyl)pyrazole-3-yl)carbonylamino]tricyclo(3.3.1.1.3.7 )decan-2-carboxylic acid (SR48692), a high-affinity neurotensin receptor 1 (NTR1) antagonist. This finding is consistent with our observation that NTR1 was localized to GABAergic interneurons in the PFC, particularly parvalbumin-containing interneurons. Because neurotensin is exclusively localized to dopamine axons in the PFC, we also determined whether neurotensin plays a role in the ability of dopamine agonists to increase extracellular GABA levels. We found that D 2 agonist-elicited increases in PFC GABA levels were blocked by pretreatment with SR48692, consistent with data indicating that D 2 autoreceptor agonists increase neurotensin release from dopamine-neurotensin axons in the PFC. These findings suggest that neurotensin plays an important role in regulating prefrontal cortical interneurons and that it may be useful to consider neurotensin agonists as an adjunct in the treatment of schizophrenia.

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Section: Expression Of Ntr1 On Gaba Interneuronssupporting

confidence: 90%

Neurotensin Activates GABAergic Interneurons in the Prefrontal Cortex

Petrie¹,

Schmidt²,

Bubser³

et al. 2005

J. Neurosci.

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“…Ultrastructural studies suggest that, in primates, DA terminals occur on GABAergic interneurons closely associated with pyramidal (output) cells (Sesack et al, 1998). Studies of the effects of DA on cortical inhibitory interneurons (Gao and Goldman-Rakic, 2003) show both inhibitory (in nonfast spiking interneurons) and facilitatory (in fast spiking interneurons) effects.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Inhibitory and Excitatory Effects of ADHD Medications Methylphenidate and Atomoxetine on Motor Cortex

Gilbert

Ridel

Sallee

et al. 2005

Neuropsychopharmacol

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Stimulant and norepinephrine (NE) reuptake inhibitor medications have different effects at the neuronal level, but both reduce symptoms of attention deficit hyperactivity disorder (ADHD). To understand their common physiologic effects and thereby gain insight into the neurobiology of ADHD treatment, we compared the effects of the stimulant methylphenidate (MPH) and NE uptake inhibitor atomoxetine (ATX) on inhibitory and excitatory processes in human cortex. Nine healthy, right-handed adults were given a single, oral dose of 30 mg MPH and 60 mg ATX at visits separated by 1 week in a randomized, double-blind crossover trial. We used paired and single transcranial magnetic stimulation (TMS) of motor cortex to measure conditioned and unconditioned motor-evoked potential amplitudes at inhibitory (3 ms) and facilitatory (10 ms) interstimulus intervals (ISI) before and after drug administration. Data were analyzed with repeated measures, mixed model regression. We also analyzed our findings and the published literature with meta-analysis software to estimate treatment effects of stimulants and NE reuptake inhibitors on these TMS measures. There were no significant pretreatment differences or effects of treatment order. Both agents produced a significant increase in facilitation and a decrease in inhibition. Effects of ATX and MPH did not differ significantly. Pooled estimates from published studies show similar results for stimulants and NE reuptake inhibitors. In conclusion, in healthy adults, both stimulant and nonstimulant medications for ADHD decrease cortical inhibition and increase cortical facilitation. Cortical inhibition, shown previously to be abnormal in ADHD, may play a key role producing behavioral pathology.

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“…First, since these neurons provide inhibitory synapses very close to the site of action potential generation in pyramidal cells, chandelier neurons are positioned to powerfully regulate the excitatory output of pyramidal neurons, and consequently to substantially affect patterns of neuronal activity both within the DLPFC and in the numerous brain regions that receive projections from the DLPFC. 8 Second, chandelier cells appear to be among the subpopulation of GABA neurons that receive direct synaptic input from dopamine axons, 9 suggesting that these neurons may mediate, at least in part, the effects of altered DLPFC dopamine function in schizophrenia. Finally, in immunocytochemical studies, antibodies against either parvalbumin or the GABA membrane transporter GAT-1 clearly reveal the distinctive axon terminals of chandelier cells.…”

mentioning

confidence: 99%